Pharmacokinetic,residue and irritation aspects of chloramphenicol sodium succinate and a chloramphenicol base formulation following intramuscular administration to ruminants

Summary

The disposition of chloramphenicol (CAP) and of its glucuronide metabolite in plasma and milk was studied following a single intramuscular injection of a chloramphenicol base formulation (Amicole^®Forte; product A) and of chloramphenicol sodium succinate (product B) to dairy cows. The dose applied of both formulations was equivalent to 50 mg CAP base/kg body weight. The HPLC determined CAP concentrations were microbiologically active. Product A revealed 30% higher plasma CAP peak concentrations (13.0 vs 9.0 μg/ml) and 36% larger areas under the plasma concentration‐ time curves than product B, whereas their absorption and elimination half‐lives were of the same order of magnitude. In the onset phase (during 4 h p.i.) unhydrolysed CAP sodium succinate could be detected in plasma and the glucuronide fraction was 26% of the parent drug. After 25 h p.i. the glucuronide fraction equalled that of the parent drug.

The maximum CAP concentration in milk was for product B equal to, and for product A 80% of the CAP plasma concentration. In milk no chloramphenicol glucuronide metabolites could be detected. HPLC methods for detecting ultra‐trace CAP concentrations in edible tissues were developed by the employment of extraction with or without a clean‐up procedure.

Seven days after i.m. administration of product A and B to calves, the CAP residue concentrations in the kidney, liver, and muscle were less than 2 nanogram/g tissue. Traces of CAP residues could be still found at the injection site and in the urine.

Chloramphenicol sodium succinate (product B) caused extensive tissue irritation at the injection site, while in the case of product A the irritation was limited. It was concluded that product A (Amicol^®Forte) had more favourable pharmacokinetic characteristics than the sodium succinate formulation.